The instruction for medical use of the drug Angal® the Trade name of Angal® the International unlicensed name Is not present the Dosage form of the Pastil for resorption with taste of a lemon Structure One pastil contains active agents: a chlorhexidina dihydrochloride of 5.00 mg (not including 3% surplus), lidocaine a hydrochloride of 1.00 mg (not including 3% surplus), excipients: aspartame, potassium to atsesulfa, fragrance lemon 501050 AP0551, magnesium stearate, sorbitol, ethanol of 96% (about/about) 1. 1 – The Description of the Pastil of round shape, moves away from white till almost white color, with taste of a lemon in the course of production. Diameter is from 15.8 to 16.2 mm, thickness is from 4.9 to 5.3 mm. Pharmacotherapeutic group Drugs for treatment of diseases of a respiratory system. Drugs for treatment of diseases of a throat. Antiseptic agents. The ATX R02AA20 code the Pharmacological Chlorhexidin Pharmacokinetics Absorption properties is badly soaked up at oral or topical administration. After local drawing on the uninjured skin, chlorhexidin dihydrochloride is adsorbed on enveloping layers of skin that results in steady antimicrobic effect. At pharmacokinetic researches it was established that about 30% of a chlorhexidin remain in an oral cavity after rinsing then chlorhexidin it is gradually removed with saliva. Speed of system absorption of lidocaine varies depending on the place and a way of introduction. It is quickly soaked up from digestive tract, mucous membranes and through the injured skin. At healthy adults the use of 2% of solution for rinsing of a mouth did not lead to emergence of the found concentration of lidocaine in plasma. At children with the weakened immunity and adults lidocaine reabsorbirutsya through a mucous membrane of an oral cavity in plasma. These values are about 0.2 mkg/ml, and toxic concentration in plasma makes 5 mkg/ml. The anesthetizing effect of lidocaine at topical administration develops quickly – in 2 – 5 minutes and proceeds within 30 – 45 minutes. Anesthesia is superficial and does not spread to submucosal structures. Distribution Chlorhexidin strongly contacts proteins in saliva. Lidocaine is well distributed on fabrics (kidneys, lungs, a liver, heart, fatty tissue). Lidocaine gets through a blood-brain barrier and a placenta and is excreted in breast milk of the person. Metabolism and excretion Chlorhexidin does not collect in an organism. It is slowly metabolized, after intake of 300 mg about 90% of the absorbed active agent are removed with a stake and less than 1% with urine. Lidocaine is metabolized during the first passing through a liver, and its bioavailability after oral administration is 35%. 90% deetilirutsya in a liver. The first two metabolites are pharmacological active. At some patients these two metabolites make toxic impact on the central nervous system. Lidocaine is removed from an organism in the form of metabolites through kidneys, 10% are brought out of an organism in the form of not changed substance. Biological semi-removal of lidocaine makes from 1.5 to 2 hours at adults. Biological semi-removal of metabolites of lidocaine happens from 2nd to 10 hours. The Lidocaine pharmacodynamics a hydrochloride represents anesthetic of amide type of peripheral local action. It has superficial analgeziruyushchy impact, without blocking carrying out a nervous impulse in the place of use. Being local anesthetic, lidocaine possesses the same mechanism of action, as other drugs of this group, it blocks generation and carrying out nervous impulses in sensitive, motive and vegetative nerve fibrils. It has direct impact on cell membranes, inhibiting receipt of ions of sodium in nerve fibrils through membranes. Due to the progressing distribution of the anesthetizing effect the threshold of electric excitement increases in peripheral nerves, carrying out a nervous impulse slows down, and reproduction of action potential is weakened that finally, leads to full blocking of a nervous impulse. In general, local anesthetics block autonomic nerves, small quicker not myelinized (feeling of pain) and small myelinized (feeling of pain, temperature), than the large myelinized fibers (feeling of touch, pressure). At molecular level lidocaine specifically blocks natrium ion channels in an inactive state that interferes with generation of action potential, preventing carrying out a nervous impulse at local use of lidocaine near a nerve. Impact on peripheral nerves is important when using lidocaine as local anesthetic. The ratio between efficiency and toxicity is favorable. The allergic reactions caused by lidocaine are observed very seldom. Besides, when blocking conductivity of peripheral nerves, local anesthetics influence all bodies in which the conductivity impulse appears. Impact on the central nervous system, autonomous a ganglion, neuromuscular connection and on all forms of muscle fibers was observed. Lidocaine is also antiarrhytmic drug of the class Ib. Chlorhexidin is encore-biguanidnym the antiseptic agent making antibacterial impact on gram-positive (for example, Micrococcus sp., Staphylococcus sp., Bacillus sp., Clostridium sp., Corinebacterium sp.) and to a lesser extent on gram-negative microorganisms, mainly on a vegetative form (at the room temperature it is inefficient concerning bacterial spores). It also possesses antimycotic action concerning dermatophytes and mushrooms. It quickly blocks infectious activity of some lipophilic viruses (for example an influenza virus, a virus of herpes, HIV). Drug works as bakteriostatik in low concentration, and in high concentrations has bactericidal effect. Chlorhexidin bears a strong positive charge, thus, it is absorbed on negatively charged sites of a bacterial cell wall and on extracellular structures. Absorption is specific and is localized on corresponding, containing phosphates, sites of a bacterial cell wall. It breaks integrity of a cellular membrane and leads to increase in permeability. Chlorhexidin is absorbed on the surface of teeth, a dental plaque or a mucous membrane of a mouth, than its long presence at an oral cavity is caused. The efficiency of antiseptic agents and disinfectants depends on concentration, temperature and time of influence. Indications Angal is the drug having analgeziruyushchy and antibacterial effect, is applied locally for: – treatment of an infection of a mucous membrane of a mouth (stomatitises, ulites) and a throat (pharyngitis) – reduction of pain at inflammation of a mucous membrane of a mouth – relief of symptoms of a tonsillitis (pain when swallowing, irritation) the Route of administration and doses of the Pastil for resorption in an oral cavity. Adults and children are more senior than 12 years: from 6 to 10 pastils a day, gradually rassasyvy in a mouth. Children are more senior than 6 years: from 3 to 5 pastils a day. Pastils are intended for resorption in an oral cavity. One pastil gradually resolves in a mouth, active agents are released slowly and gradually, having local effect. Pastils Angal are not compatible to some substances which usually are present at composition of toothpastes. Therefore, a period between use of pastils Angal and toothpaste has to make not less than 30 minutes. It is not necessary to apply pastils directly after or during meal. It is not necessary to use drug more than 3-4 days, continuously and too often. If at use of this medicine the condition of the patient did not improve or his bacterial infection is followed by the increased body temperature, then it is necessary to treat in addition an infection. The maximum single dose for the adult makes 5 mg of a chlorhexidin and 1 mg of lidocaine that corresponds to one pastil. The maximum daily dose of a chlorhexidin makes 50 mg, and lidocaine – 10 mg. Drug can be used at patients with diabetes as it does not contain sucrose. Side effects At local, limited in time, use in an oral cavity and in a throat with observance of the recommended dose drug is transferred well. Often (≥1/100, & lt, 1/10) – skin reactions of hypersensitivity – nausea, vomiting, pains in a stomach Seldom (≥1/10000, & lt, 1/1000) – heavy allergic reactions, including an acute anaphylaxis – contact dermatitis Very seldom (& lt, 1/10,000) – a small tortoiseshell It is unknown – a methemoglobinemia – the delayed allergic reaction (contact allergy, a photosensitization) or other local reactions on skin or teeth – alarm, excitement, euphoria – drowsiness, dizziness, a disorientation, confusion of consciousness (including confusion of the speech), vertigo, a tremor, psychosis, nervousness, paresthesia, numbness, spasms, a loss of consciousness, a coma – a disorder of vision, including out-of-focus sight and doubling in eyes – a ring in ears – asthma, an otdyshka, a syndrome of acute respiratory insufficiency, respiratory depression, an apnoea – difficulty when swallowing, ulcers on a mucous membrane of an oral cavity – peeling of a mucous membrane of skin, hypostasis of a parotid gland – muscular spasms or a tremor – the general weakness, temporary distortion of flavoring feelings or burning sensation in language, feeling of heat or cold At long and continuous use of a chlorhexidin in an oral cavity can temporarily appear brown coloring of teeth. However, this plaque can be removed. Descriptions of cases of decolouration of teeth at use of drug in a throat are absent. Contraindications – hypersensitivity to any component of drug – children’s age are younger than 6 years Medicinal interactions Lidocaine is well-known inhibitor of CYP1A2 liver enzyme, to a lesser extent isoenzymes 2D6 and 3A4, but interaction with these enzymes at the recommended use is clinically insignificant. It is not necessary to apply lidocaine together with other solutions to disinfection which contain heavy metals. The ionophoresis of vasoactive substances can significantly influence transdermalny delivery of lidocaine. In literature clinically insignificant interaction of lidocaine with the following medicines is described: blockers of neuromuscular carrying out, other antiarrhytmic drugs, hydantoins (antikonvulsant), epinephrine, opiates, beta-blockers, Cimetidinum and also antiarrhytmic meksiletin. At patients with the myocardial infarction caused by the cocaine use clinically insignificant interaction was also observed. Patients should not use drug together with cholinesterase inhibitors (for example, neostigmin, distigmin, pyridostigmine) or with other medicines for treatment of a myasthenia. During drug use the patients are not recommended to use at the same time other antiseptic drugs of local action. This condition does not extend to Angal®S spray for topical administration which part also is chlorhexidin and lidocaine, as well as structure of pastils. The single dose of pastils should be replaced with a single dose of spray. Patients should not exceed a daily dose of administration of drug, combining spray and pastils. It is not recommended to use a combination of spray and pastils to children. The solutions containing hlohexidin are not compatible to some types of soap and other anion-active substances (for example, alginata, tragacanth gums, almost insoluble powders, such as kaolin and also almost insoluble impurity of calcium, magic or zinc) which are usually provided in toothpastes. Thus, at least, 30 minutes have to pass between use of toothpaste and pastils Angal. Special instructions In the bacterial infections which are followed by fervescence, Angal is applied as additional medicine to reduction of a sore throat. The patients having chronic heart failure or disturbances of functions of a liver and also at the same time accepting lidocaine analogs (antiarrhytmic means of class 1B) need to be careful when prescribing drug, because of danger of strengthening of toxic effect of lidocaine. It is necessary to be careful at use of this means to the patients predisposed to emergence of allergic reactions. It is not necessary to use drug continuously, longer than 3-4 days, or it is too frequent. It is necessary to use drug only before the necessary mitigation of symptoms of pain and irritation in a throat caused by inflammation. Drug contains sorbitol, patients with rare hereditary intolerance of fructose are not recommended to take this drug. Drug contains aspartame, a source of a fenilalanilin, it can be harmful to the people having phenylketonuria. Pregnancy and the period of a lactation Use of drug during pregnancy and in the period of a lactation perhaps in cases if the expected advantage for mother exceeds potential risk for a fruit and the child. Features of influence of medicine on ability to run the vehicle or potentially dangerous mechanisms of the Research on an opportunity to drive the car or potentially dangerous mechanisms were not carried out. Overdose In spite of the fact that this medicine contains a small part of a toxic dose and use of drug is limited to topical administration, it is necessary to consider a possibility of overdose by negligence, especially in case of use for treatment of children. Chlorhexidin is soaked up in very insignificant quantities from digestive tract. Absorption of lidocaine is faster, however, its bioavailability is only 35%. The toxicity was connected with concentration of lidocaine in plasma, the exceeding 6 mg/l. After reception of overdoses (more than 20 pastils a day) disturbances from deglutitory reflexes (decrease in control over a deglutitory reflex) are possible. System intoxication is result of influence on the central nervous system and cardiovascular systems. The first symptoms of overdose are shown as disturbance from the central nervous system. The symptoms arising in system intoxication: – disturbance of the central nervous system: a headache, hallucinations, dizziness, drowsiness, arousing, sonitus, paresthesias, a dysarthtia, a hearing disorder, perioral numbness, a metabolic acidosis, a nystagmus, a muscular shiver, psychoses, spasms, an apnoea, an epileptic coma, decrease in level of consciousness, – impact on a cardiovascular system: cardiovascular insufficiency, heavy bradycardia, disturbance of a warm rhythm (stop of a sinus node, tachyarrhythmia), cardiac arrest. Separate cases of overdose chlorhexidiny are also known. In these cases the following effects were observed: throat hypostasis, necrotic damages of a gullet, increase in concentration of aminotransferases in blood serum (to 30-fold from norm), vomiting, erosion mucous in a stomach and a duodenum against the background of active atrophic gastritis, euphoria, a disorder of vision and total loss of flavoring feelings (lasting up to 8 hours). On the basis of both active ingredients given about acute, subacute and chronic system toxicity applied properly and in the concentration which are contained in pastils, the risk of mainly system effect of lidocaine can be extremely low, and is connected with serious violation of the mode of use of drug. Treatment in system intoxication: – the immediate termination of administration of drug, it is necessary to enter anion substances – gastric lavage and aspiration of contents of a stomach, to cause vomiting – hospitalization for ensuring respiratory function, prevention of dehydration and maintenance of blood circulation – in spasms is appointed diazepam. The form of release and packing On 12 pastils place in blister strip packaging from aluminum foil and a film from polyvinylchloride/polychlorotrifluoroethylene. On the 2nd blister strip packagings together with the instruction for medical use in the state and Russian languages place in a pack from cardboard. To Store storage conditions at a temperature not higher than 25 wasps. To store out of children’s reach!
2 years not to use storage term after an expiration date. Prescription status Without prescription the Producer/packer Kvalifar of H.B./C.A., Belgium Rijksweg 9, B-2880 Bornem, Belgium the Owner of the registration certificate Lek Pharmasyyutikals of of, Slovenia Verovskova 57, 1526 Ljubljana, Slovenia the Address of the organization accepting in the territory of the Republic of Kazakhstan claims from consumers on quality of medicines responsible for post-registration observation of safety of medicine Representative office of JSC Sandoz Pharmasyyutikals d. d. in Republic of Kazakhstan Republic of Kazakhstan, 050051, Almaty, Luganskogo St., 96,
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